The overall objectives of this program/project are twofold. The first is to develop methods of making human sequence variable antibody domains with combining specificity and affinity which are useful for human diagnosis and therapy. The second objective is to produce protein molecules which have defined amino acid alterations within the combining site so that methods of predicting the three-dimensional conformation of a small portion of this protein can be tested, modified and improved. Chemical synthesis of the DNA to code for complementary determining regions of the light and heavy chain variable regions will be combined with framework DNAs by using overlapping nucleotide sequences with suitable restriction endonuclease sites to make complete VL and VH genes. The medical uses of the material thus obtained would be for: (1)\combining with and eliminating a drug after the desired treatment time in cancer chemotherapy; (2)\eliminating from the serum any undesirable small molecules resulting from drug overdose; (3)\localizing by means of radioiodine coupling any identified cancer antigen; and (4)\possible elimination of various receptors leading to the immediate allergic response. During the past years, clones have been isolated containing cDNAs of both mouse and human immunoglobulin chains. These are now being sized and sequenced. cDNA molecules representing complete heavy and light chains, as well as complete variable regions, will be inserted in various expression vectors with the aim of obtaining secreted immunoglobulin. The program/project involves the collaborative work of several investigators.